The present invention relates to a vaccine for the prevention of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). In particular, the present invention relates to a synthetic peptide which may be used in a method of immunization against AIDS and in a diagnostic assay for AIDS.
AIDS was first discovered as a severe immune deficiency which resulted in reports of opportunistic infections occuring among male homosexuals (see Gottlieb, M.S., et al., 305 N. Engl. H. Med. 1425-1431 (1981) and Masur, H., et al., 305 N. Engl. J. Med. 1431-1438 (1981)). The incidence of this new human disease, named "acquired immunodeficiency syndrome" (AIDS), is rapidly growing. Although sexual transmission appears to be the primary mode of transfer, a number of cases in which the disorder was transferred by blood transfusion have been reported (see Gottlieb, et al., supra). The etiologic agent of this disease has been shown to be a human retrovirus, known variously as human T lymphotropic virus type III (HTLV III), lymphadenophathy-associated virus (LAV)(Barre-Sinoussi, F., et al., 220 Science 868-871 (1983)), or AIDS-associated retrovirus (ARV).
Seroepidemiological studies have identified HTLV-III--specific antibodies in the serum of most patients with AIDS or ARC. The predominant antigens recognized by antibodies in sera obtained from AIDS patients and from hemophiliacs are associated with the envelope glycoproteins. Further, the most immunogenic proteins of the human T lymphotrophic viruses, HTLV-I and HTLV-II are cell surface-expressed glycoproteins (Chen, I.S. et al., 305 Nature (London) 502 (1983)).
The envelope (env) gene product of HTLV-III is synthesized as a polyprotein precursor and is subsequently glycosylated within infected cells This glycosylated glycoprotein, with an estimated molecular weight of 160K (gp 160) is processed into gp 120 and gp 41 subunits. The gp 110 glycoprotein of LAV appears to be the same protein as gp 120. This gp 41 subunit is one of the predominant polypeptides in purified virus preparations.
Antibodies from AIDS and ARC patients contain viral neutralizing activity; however, infection presumably occurred in those patients prior to the development of neutralizing antibody. The general notion with retroviruses is that the antigenic determinants or epitopes associated with the induction of neutralizing antibodies are associated with the glycoprotein envelope (see Holden, H.T. and T. Taniyama, 150 J. Exp. Med. 1367 (1979) and Flyer, D.C. et al., 305 Nature (London) 815 (1983)). As will be described, it has now been demonstrated that the gp 41, gp 120 and gp 160 envelope glycoproteins are the most immunogenic epitopes in virus-exposed individuals. The present invention is premised upon the assumption that the critical epitopes involved in the induction of protective virus neutralizing antibody are associated with the two viral envelope glycoprotein subunits, gp 120 and gp 41.